It is proposed to analyze the genetic structure and, in particular, the transforming onc genes and proteins of avian and murine retroviruses and of their cellular prototypes, termed proto-onc genes. Viral onc genes consist of specific elements derived from cellular proto-onc genes as well as from retroviral genes. For this reason, it is now widely believed that proto-onc genes can function as cellular cancer genes upon transcriptional or mutational activation. This project will analyze common and specific properties of corresponding onc genes and proto-onc genes, in order to determine whether and under which conditions proto-onc genes may function as cancer genes. The studies will first involve structural analyses of onc genes and proto-onc genes. Subsequently, the function of structurally defined onc- and proto-onc gene domains will be analyzed in viral vectors by deletion analyses and by in vitro recombination analyses between the onc genes of cloned retroviruses with corresponding proto-onc genes.